WASHINGTON, D.C.—With the U.S. healthcare reform law giving U.S. regulators a legal framework and authority to develop an abbreviated approval pathway for biosimilars—off-brand versions of biotech drugs—the U.S. Food and Drug Administration (FDA) is still navigating these as-yet unchartered regulatory waters. To answer some of the FDA's nagging questions, the Brookings Institution, a nonprofit public policy organization, held a hearing Dec. 1 to discuss key implementation issues associated with biosimilar entry in the United States and what the government's role should be in regulating the process.

The hearing, called "Biosimilars in the United States: Implementation Challenges and Lessons Learned from the European Union," addressed regulatory and implementation challenges and opportunities and provided a comparative analysis of the European Union's experience in creating a biosimilars approval pathway.

The European Union, as well as several countries around the globe, has already implemented an approval pathway for biosimilars, but it wasn't until the passage of last year's Patient Protection and Affordable Care Act that U.S. regulators began taking a serious look at implementing a process by which to approve the development of biosimilars here.

Among the questions facing the FDA are how to identify and monitor adverse events, what kinds of clinical data are required for approval and how to involve the various relevant stakeholders in these decisions.

The panel of experts was moderated by Brookings Vice President and Director of Governance Studies Darrell West. Speakers included Anthony Ridgway, a senior regulatory scientist at Health Canada; Mary Pendergast, president of Pendergast Consulting, which provides strategic and tactical advise to biotech and pharmaceutical corporations, governments, professional and patient groups and institutions on regulatory issues relating to compliance and drug development; and Henry Grabowski, professor of economics and director of the program in pharmaceuticals at Health Economics at Duke University.

Ridway said that in Canada, biosimilar products are examined "on a case-by-case basis."

"Full chemistry and manufacturing data is required, plus the comparability study with the referenced biologic. Clinical data is required. The amount of that data is negotiable and is influenced by several factors. And one should use the same reference product throughout the development of the program," Ridway explained. "On the Canadian side, we started with a new drug submission approach and said, okay, what concessions, what relaxations can be made. And I think it's interesting that both the European Union and Canada have ended up around the same place, even though we perhaps approached it from different directions."

Grabowski said there are many lessons to be learned from Europe.

"Germany is the kind of leading edge of usage of biosimilars, and basically they have had biosimilars for erythropoietin now for two years and for the G-CSF's products like Neupogen for one year," he said. "And the penetration against the reference product, Eprex in the EPO area is now at 60 percent. We're seeing price changes. The price discounting of the biosimilar relevant to the reference product, that introduction is now around 40 percent. And we also see the reference product dropping its price, not the full 40 percent, but a significant amount, part of the way towards the biosimilar in Europe, and that's all without any kind of substitution or interchangeability."

Data exclusivity, one of the main points of debate in legislators' ongoing discussion about approving biosimilars, remains an issue, Grabowksi added.

"People say, well, if we have patents, why do we need some period before the data exclusivity, it's the period before a biosimilar can rely on some of the initial safety and efficacy data to get an abbreviated approval," he said. "Congress eventually settled on 12 years after a lot of debate. Should it be 5 years? Should it be 14? Some say we don't need it. I think the reason you need some kind of exclusivity is often the drug candidates, the good drug candidates, good therapeutic candidates may not have good patent protection. It may take a long time so that the core patent time is eroded."

Speaking candidly about the motivations behind defining an approval pathway for biosimilars, Pendergast said, "I think the one thing you can say about the United States is that the biosimilar legislation was definitely economically motivated, and there certainly has been enough politics in it for everyone to have a share. Should we envy our Canadian neighbors to the north, where this was not either politically nor economically motivated?"
In the United States, Pendergast said, questions about the regulation of biosimilars remain across multiple government entities.

"So talking about the implementation of biosimilars, I was at the FDA, worked on the Hatch-Waxman legislation before it was passed, and then helped implement it. I litigated the first case under that legislation and have watched it over the last 26 years. And one of the things I would like to point out is that 26 years later, there are still court cases, there are still guidance documents coming out, there are still areas of that law that we don't understand or where courts have taken contrary positions," she said. "You have a seminar next year at this time, do not expect everything to be decided, because it won't have been."